BreatheTV Episode 15

Transcription

Michael McQueen: Thank you. Good afternoon everyone. My name is Mike McQueen. By way of disclosure, I am the Vice President of Medical Education for Vapotherm. Prior to that I was in clinical practice for 27 years as a neonatologist at various level 2, 3, and 4 NICUs. The purpose of this round table… And in a moment I’m going to let the guests introduce themselves… The purpose of this discussion panel is to simply discuss the role of high-flow therapy in the management of the neonatal patient in the NICU. We’ll hit on as many topics as time allows, and I want to thank all of you in advance for your time and expertise for being here. So why don’t we start with introductions.

Amir Kugelman: Hello. My name is Amir Kugelman. I am the head of the neonatal department in Rambam Medical Center in Israel. I did my fellowship in LA, and I’m a Neonatologist and Pediatric Pulmonologist, and I’m happy to be here. So we’ll discuss our experience with Vapotherm and maybe other modes of noninvasive intubation.

Brad Yoder: Hi. My name is Dr. Brad Yoder. I’m the Division Chief at the University of Utah, Division of Neonatology. I’m also a Professor of Pediatrics there. I’ve been in practice for over 30 years with my training in neonatal and perinatal medicine. My predominant interests are in a variety of lung diseases, in particular BPD, and then the support of babies with a variety of different types of interfaces including high-frequency conventional ventilation, and noninvasive forms of support including high-flow nasal cannula.

Brett Manley: Hi. I’m Brett Manley. I’m a Neonatologist from Melvin, Australia. My interests include noninvasive ventilation of the preterm baby and ways of reducing BPD in extremely preterm infants. In Melvin, we’ve been involved with multiple studies of nasal high-flow including three large randomized trials of nasal high-flow use in neonatology.

Michael McQueen: Great. Thank you, gentlemen. Dr. Yoder, I’m going to start with you. This panel here is four-sevenths of a consensus group that you put together to discuss finding common ground on the use of high-flow in the NICU. Can you tell us the rationale for that paper and what some of the common findings were?

Brad Yoder: The rationale. Yeah, why take on that effort? I think the main reason I wanted it to do is because I kept hearing in a lot of discussions with people in a variety of places, either in the hospital or conferences, that they were using high-flow but, they were using it this way or that way, and they weren’t sure what to do. They weren’t sure where to start. They weren’t sure what device to use sometimes or when to use it. And I thought what we needed was an attempt with some guidelines to establish what evidence we did know was out there, and what seems reasonable in terms of how to approach high-flow. What systems should be used? What flow rates could be potentially used? How do you increase it or decrease it? And just see if we could, with a collection of people who had spent time investigating and had a lot of clinical experience with that, what was working, what the evidence was.

Brad Yoder: In part, by doing that, we could then also establish areas where research was needed. Where we just didn’t have a good consensus and that would give people, then, an opportunity to think, “Okay, these are types of questions that haven’t really been well answered or we don’t have good evidence for.” So it would be, if you will, a board to kind of jump forward and move towards doing new studies, better new trials.

Michael McQueen: Outstanding. Well thank you for your effort in doing that. And again, could you touch briefly on what you thought the greatest areas of consensus were?

Brad Yoder: Well, I think we all agreed that the best consensus was humidification and heating. Proper heating, proper humidification of gas, particularly at high flows, was absolutely critical and had to be maintained. We also agreed, although there’s not really the evidence overwhelmingly to support it, that the maximum flow the baby should get would be about eight liters. And that was for the neonatal period. There is a different approach in older patients and in pediatric and adult patients. But we haven’t investigated higher flow rates than that in the neonates.

Brad Yoder: We agreed that it was a reasonable intervention, in comparison to CPAP alone, for the support of babies who were being extubated after having been intubated and having management of their respiratory problems. And that in terms of the overall approach to high-flow, I think we all came to an agreement that we should treat it kind of like CPAP. It’s a noninvasive form of ventilation, and if you have signs that the baby is not doing as well as he should be as- he had increasing retractions, or increasing work of breathing, or increasing respiratory rates- that more support might be indicated. As well as if FiO2 needs were going up that more support might be indicated. And then again, if that wasn’t working, then you needed to think about other options.

Michael McQueen: Thank you. I heard your-

Brad Yoder: Is that about right?

Brett Manley: That’s about right.

Michael McQueen: Thank you again. I heard your emphasis on post-extubation support. Brett, one of the more, I think, widely cited studies as I travel around in my new role, is the Hipster Trial and the stark difference in high-flow versus nasal CPAP as a primary therapy modality. One of the overlooked pieces, I’ve always thought, of the trial was the fact that if you have a CPAP backup, the rate to intubation and that kind of invasive support didn’t seem to differ that much. Could you elaborate on that piece?

Brett Manley: Absolutely. So, the Hipster Trial was a multicenter randomized trial, performed in tertiary NICUs in Australia and Norway, that recruited preterm infants born between 28 and 36 weeks of gestation. So, importantly, there were no extremely preterm infants eligible for the trial. And in that trial, as early respiratory support, either directly from the delivery room or in the first hours of life, infants were randomized either to nasal high-flow, six to eight liters per minute, or to nasal CPAP, six to eight centimeters of water. And the primary outcome in that trial was treatment failure based on objective treatment failure criteria. In that trial we showed that high-flow was inferior to CPAP at preventing treatment failure. The rate of treatment failure was approximately 20% in the high-flow group versus 10% in the CPAP group. That was a 564 baby trial that was actually stopped early because we had clearly defined the result of the primary outcome in the trial, that CPAP was better than high-flow at preventing treatment failure.

Brett Manley: But what might point out is true, is that once an infant had satisfied treatment failure criteria and therefore the primary outcome in the trial, they could be offered rescue CPAP. And that high-flow plus CPAP backup regimen meant that the secondary outcomes were very similar between the groups. In fact, there was no difference in the rate of intubation and mechanical ventilation, or in any other important respiratory type outcomes.

Brett Manley: So I think we’re in a little bit of a conundrum there, in the sense that, if the question is: “Is high-flow as good as CPAP for preventing treatment failure in the first hours or days of life in preterm infants with respiratory distress syndrome?” the answer is no. CPAP is better in our trial. The way we did it. But high-flow plus CPAP backup seems to be a perfectly efficacious and safe way of treating infants. The question would be: “Why would you choose to do that?” and centers might. They might prefer high-flow, which works most of the time in most of the babies, and they might have access to multiple modes of support. So it all comes down to how you do things, cost effectiveness. Money is important here. Are you going to buy both modes of support, or are you just going to buy one that works better? And there are the decisions that clinicians need to make.

Michael McQueen: Great. Amir, anything to add first, before I ask you about your trial, to the discussion so far? Anything you would add to any of the comments?

Amir Kugelman: Just to hear the consensus was very important because the high-flow went into practice before the studies came out. There needed to be some kind of consensus in order to learn from all the studies that were done. And the consensus people who are involved with these studies, come out of some form of treatment that we can adopt, that were evaluated by randomized control trials because everybody was doing high-flow without really without good data as a baseline. So it was very important to get out the consensus. In the future the studies will tell us if the consensus was correct or if we have to improve it.

Brett Manley: Brad, can I ask you a question without notice? In your randomized trial of high-flow compared to CPAP, a very pragmatic trial, babies were eligible regardless of the indication for noninvasive support, you showed that they seemed to be quite similar in their efficacy. Including in, I think, about one-third of babies that received support as early support, or was it the other way around? Which one was post-extubation?

Brad Yoder: Yeah, it was just about 30% received it as the initial support.

Brett Manley: And that was with lower flows than we’ve used in subsequent RCTs and yet seem to perform better. When you read our studies, how do you reconcile those two results?

Brad Yoder: Well I agree that we did start with lower flows, but we had a mechanism that allowed for escalation of flow, with a maximum of flow going up to as high as eight liters in the bigger babies. It depended on the size of the baby, how high we would go. At that point in time it was a safety consideration. We just didn’t have enough data or enough evidence in our mind. Even though, quite honestly, I’d been using high-flow for almost eight years in a different environment, that I was convinced that the higher flows weren’t necessarily safe. We opted to start lower and escalate up to a certain level without going above. For example, we didn’t go above six liters in some of the smaller babies even though other trials have started at higher flows and appeared to, fortunately, in their randomized trials, they now have evidence that there wasn’t any increased risk. If I were to do it again I would probably reach a maximum for everybody that’s probably the same.

Brad Yoder: But we did have a higher failure rate, actually, with both high-flow and CPAP in the arm where we started with that support as a primary therapy as opposed to a post-extubation therapy.

Amir Kugelman: If I may just add to this, we also started with low flows because there was no baseline that time. You were worried about [inaudible] and air leaks. So just to add for this discussion, that it’s very important when you use the high-flow to keep the leak. It’s not the same, like CPAP or NIPPV, where you measure the pressures. When you use the high-flow, there’s no measurement, so you have to be very careful to allow the leak. This will make all the difference. When we started our studies, there were no studies published, so we started low and went up. And still it might be a question whether it’s possible, if the baby does not need a lot of flow, to start low and go up even at first, but to start high and wane, or maybe wean the baby off the high flows immediately to slow down their breathing. There are no good data to support each of those options.

Michael McQueen: Where do you start your flows now?

Amir Kugelman: Now we are starting … It really depends. Usually we don’t start … It really depends. If you are starting for initial therapy, we only start on babies who don’t have significant respiratory distress or significant RDS. In extreme premature infants, we only start with NIPPV not with high-flow. If we go to high-flow, it’s for post-extubation, and we go between four to six, still now. We go higher only if we need. Most of the babies will manage with this flow.

Michael McQueen: Brad, you see anything different?

Brad Yoder: I wouldn’t say much different. We typically start … So A) We do not use high-flow for primary disease. We use CPAP or noninvasive ventilation, and then transition to high-flow. Something I should probably query that. There are some babies that we think really just have some transient tachypnea. We would use high-flow in that subgroup of babies. But usually we start in the four to six liter range. With four for the smaller babies and six for the bigger babies. Then that just gives us an opportunity to go up.

Brad Yoder: One of the reasons I like to start there is because a problem that happens is people get on flow, and it happens with CPAP as well, you get on a flow or CPAP level, and they don’t wean. I think it’s just like being on a ventilator: If you can wean off, you should wean off. By starting at a little bit lower, they’re gonna wean off earlier rather than not. But if they have to escalate, well then that’s fine.

Michael McQueen: Interesting. Brett?

Brett Manley: Well as time’s gone by, we’ve become more and more comfortable with higher flow rates, such as we’ve used in our randomized trials. We start, for whatever indication, usually six or seven liters per minute. We go up to a maximum of eight, if required, and if that wasn’t working we’d look at the baby, look at the oxygen requirement, and consider whether high-flow was not the right mode of support, and we needed to change to CPAP or some other mode.

Brett Manley: In terms of weaning down, I agree that’s a critical issue in how we use all of our noninvasive support and mechanical ventilation. BPD is an ongoing big problem. The definition of BPD has flaws, I agree, but I think as clinicians it’s our responsibility to get babies off support if they don’t need it. So I agree with Brad and Amir, if a baby has clinically improved with a short-term respiratory condition, we would stop from whatever flow the baby happened to be on at the time. In the babies that need more ongoing support, we would wean by a liter per minute up to once or twice a day, depending on how the baby was doing. Generally slower in the tiny babies and quicker in the bigger babies. And when we were happy with the baby’s condition, we would either… We would stop it. If we wanted to provide ongoing support we would go as low as four liters per minute, and no lower, and then stop the high-flow.

Michael McQueen: So, four was your floor?

Brett Manley: So, we started out in our early trial, we went as low as two. I think that’s unnecessary, and I’m concerned, personally, that anything down in that flow range is not providing very much support. It depends what you’re using it for. If you just want to provide oxygen, then it will do that. But I think if you’re calling it respiratory support, I think anything less than four, there’s some evidence to suggest that there’s not much support going on. And taking into account the fact that we need to wean babies off, it’s very important to stress that there’s no need to wean the babies all the way down. And that’s why we’ve increased our minimum to four to at least harshly rectify that situation.

Amir Kugelman: Just to add … It’s very important when you’re doing rounds, and the babies are stable, to keep in mind, don’t just sit there with the baby if it’s possible. Because studies are showing that because we are comfortable with the high-flow, babies take more time on nasal support. Saying that they stay in our unit, if the baby is on four, for example, we weaning instead of going to nasal cannula without flow. Because this is humidified and warm, and still the high-flow is better than regular cannula.

Amir Kugelman: So if we have enough Vapotherm, so you’re using the Vapotherm for high-flow, then I don’t see why you’d take the baby off the Vapotherm if he’s going to get two or three liters by nasal. So we still wean the babies up to two, even sometimes to one liter, and it’s a way of giving the oxygen, but in a safer way to protect the airways. If we have shortage of the vapor, then we take the babies off. But the idea is, it’s still safer and better for the airway to have warm and humidified air, even if it’s low flow. We don’t call it high-flow, less than two liters considered low flow, but still we use it because a good method of supporting the baby.

Brett Manley: Yeah, I agree with that practice. In our center, low flow is quite low. We would heat and humidify anything over about 200 or 300 mils per minute, actually. Most of our babies aren’t on a liter or two liters of unhumidified. So, I agree we would preferentially use high-flow in that situation. More and more of our extremely preterm infants with evolved necrotic lung disease, who have an oxygen requirement, are staying on high-flow until their 34 weeks gestation, and then we try to switch it to low flow.

Michael McQueen: Good. One of the statements, Brett, that you made that I agree, all of us agree whole-heartedly with, is it’s our obligation to minimize support in whatever way we can and minimize the invasiveness. Towards that end, one of the differentiators in the trials that have shown clearer inferiority of high-flow to nasal CPAP, and the ones that have not, has been the inclusion of surfactant before the primary outcome measures. I’m thinking specifically of Lavizarri’s trial and of Kugelman’s trial. And since you’re sitting here, go there, tell me about the role of surfactant.

Amir Kugelman: Well, basically, I want to say two things about it. First, I believe, and the studies show, that NIPPV is better than CPAP for initial treatment to prevent intubation and post-extubation. I think the goal in future studies will help evaluate high-flow versus NIPPV, not only against CPAP cause raising our hands NIPPV is better, and it was shown also by Cochrane analysis.

Amir Kugelman: And my study was to compare the high-flow, comparing it to NIPPV. In both our studies, CPAP versus NIPPV and NIPPV versus high-flow, we didn’t give surfactant before using the NIPPV. It was an initial mode. This is, of course, to the study of Lavizarri, where she gave the surfactant. So, this might change the etiquette because maybe the surfactant is helpful, and the results might change and high-flow may get placed. But in our study, we used for initial treatment, NIPPV versus high-flow. And surprisingly, I would say, because I was expecting to have better results with the NIPPV, there was no difference between the group. But the study included only around 80 patients, around 40 in each group, and it was relatively larger babies. So I think we need more studies on extremely premature infants and infants who have more severe lung disease.

Michael McQueen: Great. Brad, go there on surfactant.

Brad Yoder: Well, you know, it makes to study design. So, it complicates things. I think, to me, a more pure study would be to say: “Okay, we’re going to randomize to either CPAP, NIV, or high-flow, post-surfactant therapy.” So it becomes more like an INSURE Methodology where you’re saying: “Okay, we’re managing our baby noninvasively with whatever, but now once we’ve said we’re going to give them surfactant, now let’s randomize them to one arm or the other.” And there are, I think, one or two trials out there which actually have looked at that, that are small, that suggest in the face of that there’s probably a similar type of outcome.

Brad Yoder: The problem becomes … It’s just confusing to me, to say: “We had similar outcomes.” … The problem I have is failure. To me, if you have to intubate a patient and give them surfactant, they have failed your therapy. At that point in time, it now becomes a different study. I think it’s very important for people who are using any of these things that they really critically analyze the study populations that are involved in whatever study. Cause the Hipster had a slightly different study population, in terms of the respiratory support that was required, than Anna Lavizarri’s study had, which tended to have a higher … So there was a higher failure rate in her study relative to Brett’s study, but there was a difference in the population also that was being looked at. So it’s really important to look at those and then look at how you’re applying it in your own practice.

Amir Kugelman: It’s very important, especially when you look for the long-term, the BPD. We notice that if a baby was intubated and got positive pressure ventilation via ET tube, it affects the long-term outcome. A lot of studies are doing some combination of noninvasive and surfactant. If the baby was intubate … And they say the CPAP and NIPPV does not affect the BPD rate. But still if you intubate the baby, it might have an effect.

Amir Kugelman: In any case, in most of the studies, we support the baby. Some studies for three days and then the babies go to any other mode: CPAP or NIPPV or seven days. If you have a 24 week and after three days, seven days, you change the mode of ventilation, then you can’t look at long term because the babies are not on the same mode for a long time. So we have to clean the studies, and to evaluate studies who are clean. Surfactant, no surfactant. Intubation, not intubation … You can’t call a baby that’s not intubated because intubated only for less than 24 hours. It’s really important to have clean data to come out with good conclusions.

Michael McQueen: Yeah. Brad, do you use the INSURE Method, when you have to intubated for surf then you take them right back off of it?

Brad Yoder: Do we use the INSURE Method? Yeah, we do. We’re pretty comfortable with that. But I will say that as of right now, our general approach is that we … If we intubate a baby to give them surfactant, we actually extubate them to CPAP.

Michael McQueen: Okay.

Brad Yoder: And then they would transition, at some point, to high-flow or if they have a really positive response they may end up on a regular cannula.

Michael McQueen: Yeah, absolutely.

Brad Yoder: That’s our current approach.

Michael McQueen: Brett, your current practice, when they reach treatment failure as you’re defining it now, I’m gonna push back on that just a little bit … Recognizing as another disclosure that when this is over I’m going to get all three of your autographs. You’ve contributed more than I will ever contribute, and thank you for that … But treatment failure, if you have to intubate to give surfactant, do you leave the tube in?

Brett Manley: At the moment, we do. That’s been our practice. Now, we’re part of a randomized trial looking at a way of giving surfactant with minimally invasive technique or less invasive technique, if that’s what you’d like to call it. So some babies are in that randomized trial. But our standard practice in extremely preterm babies would be to intubate them and leave them on a mechanical ventilator, but with the aim to get them off as quick as we could. The reality is that, that’s normally a day or two, before they actually get the tube out. So it’s not an INSURE Method, per se. I think the way of the future would be less invasive surfactant administration or minimally invasive surfactant … We’re just in a randomized trial. We’ll get that done and then we’ll make our decisions about how we are going to approach that situation.

Brett Manley: On the topic of surfactant, I absolutely agree with Amir and Brad, that as soon as you give a baby surfactant, it’s a different baby, and you can’t log trials that have given surfactant or haven’t all together. I think we have to be very mindful of that going forward, with updating the Cochrane Review and meta-analyses, how we treat different trials that have or haven’t used surfactant or allowed surfactant.

Amir Kugelman: Yeah.

Brad Yoder: Yeah.

Michael McQueen: I couldn’t agree with the three of you more on that. It is a different patient once you’ve administered surfactant. In my mind, that’s kind of the whole point. I’m not-

Amir Kugelman: Especially if you’re doing it for … Especially if you administer surfactant via ET tube because correct ventilation of the baby is changed. And we know the studies that infuse via ET tube makes a difference.

Michael McQueen: I’m old enough, I’ve been in practice long enough that I practiced before surfactant was available as a tool. And I certainly don’t wanna go back there again. I’m not sure, in my mind, that I’ve ever considered having to give surfactant to a surfactant deficient infant, a treatment failure. I don’t think I would say that. I can’t … It certainly from trial design, you’d design it as you see fit and as a primary outcome I understand that completely. From a pragmatic, at the bed-side standpoint, I’m not sure why I wouldn’t give surfactant deficient infant surfactant. And I would do it sooner. I’m not gonna let him get respiratory fatigue or damage lung tissue as exposed to higher volume trauma and FiO2 both in doing that.

Michael McQueen: Brad, when you do it, how early are you giving it?

Brad Yoder: It’s quite variable. It’s extremely variable. I wish there was a consistent approach. We’ve certainly tried to build written guidelines in our units for all of these things but-

Michael McQueen: It’s our next consensus maybe?

Brad Yoder: …everybody kind of takes their own approach as to does this meet our criteria or not. I think we’ve inched down some, in terms of … If they’re on a significant amount of CPAP support and their FiO2’s creeped up, used to be up to 50 now we’re actually down to 40, we might as well give it to them earlier rather than later. Particularly in the more mature baby. Now in the more immature baby, we actually probably end up doing more of what Brett does. They get surfactant in their 24, 25 weeks. Even 26 weeks, they’re probably gonna stay intubated for a longer period of time to make sure that they have the responses, to make sure they have the respiratory drive, and then be subsequently extubated. So, in the very small babies, if they end up just wearing out, they get tired … Whenever they get intubated they get surfactant. It’s just-

Michael McQueen: Fair enough.

Brad Yoder: …what they’re gonna have.

Michael McQueen: Amir, your criteria? What do you do?

Amir Kugelman: Well, we try to have some protocol. The idea is after delivery the premature infants, the smaller ones, are going on NIPPV. If the baby is about 30%, we are trying to give less invasive ventilation and surfactant therapy, and then we try to take the babies off. If the baby were not placed in the study, and we are using the less invasive only within a study, the baby goes between 35 to 45% by using the INSURE. And if the baby does not look stable while we are doing it or some practical issues … If it’s during night time or if you’re not sure about the resident who is going to stay with the baby- because we have residents at night- but maybe the baby might stay on the vent until the next day. And then the next day, it really depends not only on his lungs but depends how active the baby. If we see that the baby can be taken off the ventilator or he should stay.

Amir Kugelman: But the idea we are trying to use less invasive surfactant therapy only within a study, if not we are trying to use the INSURE, but within practical situations. You have to remember that not only a study. We are taking care of babies.

Michael McQueen: Well said.

Amir Kugelman: Some people are younger than others, and we have to consider this.

Michael McQueen: Well said. Yeah, you’ve all alluded to the importance of respiratory drive. I guess that’s a given that maybe we shouldn’t assume in this format is a given everywhere. The single biggest contraindication to high-flow is that it is lack of adequate respiratory drive, in my mind. I think that’s why the 24 and 25 weekers are a whole different population. Then I would concur, if those babies need elevated support or escalated support, I would wager most of us would do the same thing and leave them on that support longer. So good distinction on that.

Amir Kugelman: I think we have to remember that the high-flow, even when we give CPAP, it’s not exactly like CPAP, with CPAP and NIPPV, because we keep a leak. This is by definition, this is what accommodation is. If the baby have significant RDS, if it’s extremely premature infant, I think it’s understandable the CPAP or NIPPV are better than high-flow. We don’t have studies on the smaller infants, but even on the bigger infants it’s still shown that CPAP is better than high-flow.

Amir Kugelman: If we are ready to allow the baby to fail and escape to or rescued with CPAP and NIPPV it’s okay. But I usually don’t like very extreme infants to fail. You don’t know if they fail, if the lung collapse it might be demanding enough to open the lungs since we are not sure what’s going to happen. This is in the first three days of life is a problem with IVA, and you don’t want to play with the baby. You don’t want it to fail. We want to keep as much as stable baby if it’s possible. So the option of rescue in smaller premature infants, I’m not sure if it’s safe enough, but we don’t have data on this. On bigger infants it’s an option. And really we don’t have an option for the most extreme infants with rescue therapy.

Michael McQueen: One more question on this, then we’ll switch topics a little bit. Tell me where you draw that line, Amir, between smaller infant and bigger infants. And then I’m gonna ask both of you the same.

Amir Kugelman: Most of the studies on high-flow are done on infants that are larger than 1000 grams. Most of the studies are done on those infants. Even in the Hipster, the infants were relatively large ending up the difference. Right, Brett? The infants were relatively large. I think 24 up to 27 weeks are, for me, still extremely premature infants and I would … Even below 28 I would try to use NIPPV and CPAP instead of high-flow as initial therapy.

Michael McQueen: Good. Brad?

Brad Yoder: Yeah, I think my interpretation of the data that’s out there to date is that the best … What we do is we will not usually offer high-flow as a primary therapy to babies less than 28 weeks. They can eventually get on to that, depending on their course, but we don’t use it as the primary support. That’s perhaps my biased interpretation of the literature as well as my biased interpretation of our clinical practice.

Michael McQueen: Fair enough. Brett, same question.

Brett Manley: I totally agree. There’s a paucity of data for extremely preterm infants for the efficacy of high-flow. We would use CPAP as our first-line, noninvasive support for all of our extremely preterm infants. Also, after extubation, we would extubate extremely preterm infants to CPAP or NIPPV. We’ve seem fairly consistent on that.

Brett Manley: In terms of primary support, we’ve got the Hipster Trial and the Hunter Trial coming, and I think we’ll wait to see the results of that to get a better … At the moment, I wouldn’t recommend using high-flow as primary support for preterm infant with RDS, based mainly on the results of Hipster. Whether there are some infants that high-flow may be highly successful in, is something that we’re trying to tease out now. Are there ways we can predict which babies need the CPAP constant distending pressure versus might be alright on the high-flow. I think we’re still working our way through that. So, as it stands, CPAP for me.

Michael McQueen: Great. Thank you all very much.

Michael McQueen: Completely different topic … I get asked this all over the country when I travel, can you feed babies on high-flow? Especially now that there seems to be some consensus that high-flow means five liters, six liters, even seven and eight liters per minute, on some pretty tiny babies. Do you feed them and how? Brett, let me start with you.

Brett Manley: Firstly, I’d say there’s no large randomized trials of feeding babies on high-flow versus any other mode of support. When you do look at the randomized trials that have been done, though, there doesn’t seem to be any problem in terms of high-flow use and nutritional or weight outcomes. In our unit, which is anecdotal, we are very comfortable with babies suck-feeding either at the breast or the bottle on high-flow at any flow ratio. So, if they’re ready to have suck-feeds and they’re on high-flow, they have suck-feeds.

Michael McQueen: Great. That’s very reassuring to hear. Brad?

Brad Yoder: Yeah, that’s a great question. There are no large randomized trials. There was actually a study that is presented in a poster-form, I believe, at this meeting comparing high-flow to CPAP and the ability to effectively oral feed. Basically, as I recall, suggested they were probably fairly similar. But it’s completely dependent upon the patient, and their readiness, and their ability. I think we just need more information.

Brad Yoder: We do PO feed some of our babies who are on high-flow. Most of them tend to be the larger babies, so 34 weeks and above, who clearly have good cues, are on it and are stable. We’ve done it up as high as six liters. We typically … Our feeding specialists, our speech therapists, occupational therapists, they push me to say: “Why don’t you wait until he gets to three liters, or two liters, or whatever.” But I say: “If he’s ready to go, he’s ready to go.” And if he doesn’t do well, then that’s when we can pull back. I would like to see more investigations about particularly using techniques that can actually assess the suck-swallow technique. As well as a randomized trial that has a specific population data set that says inclusion/exclusion criteria. Really give us an idea of whether it is or is not (A) effective and (B) safe.

Brett Manley: And hearing you say that, I should probably add the caveat that whilst I said we would feed babies on high-flow, that’s true. By the time they’re getting ready to feed, and we’re in the 34-35 week range, it’s very rare for a baby to be on high-flow at a high flow rate. They would generally be towards the lower rate of our spectrum- four, five, or six liters- at that time. Mainly the sicker babies are still on CPAP in our unit. I think that’s important to say, that whilst I said that you can feed a baby on high-flow, the truth is most of them would be on that medium to low flow rates.

Michael McQueen: Before I get to you, Amir, some of the places are even asking about gavage feeds on high-flow. Any issue with that?

Brad Yoder: Our emphasis is to increase enteral feeds as quickly as possible, and we don’t have problems with that.

Michael McQueen: Amir, your practice?

Amir Kugelman: Two factors are playing a role. First, the acuity of the distress of the baby on high-flow and still in distress is not getting PO feeding. Cause it can’t eat PO in any mode. Even if he’s continuously breathing but the rate of breathing is sixty-eighty, he’s not getting PO feeds. Usually, this time when the baby is ready to be fed, and it still needs high-flow, it must be a baby who is chronic, like BPD patients, and those we are allowing them to feed PO if they have the possibility eat, if they want to. This is still anecdotal because if he is BPD and he’s not in distress, and it can try to feed, we allow them to do it. But it’s still for bigger babies and not in the acute stage.

Michael McQueen: Great. Thank you. Tina just gave me the heads up that we’re a little over thirty minutes, and I made a time commitment to you all. So, I’m going to ask one more question, and then we’ll stop. Tell me … Delivery room management, I’m clearly interested in the role of high-flow in the delivery room, but independent of that, what do you do? Brett, start us.

Brett Manley: Now that it’s on my mind, I might mention that there are some centers around the world who are using high-flow in the delivery room to stabilize even extremely preterm infants. I know Peter Reynolds and the group from Surrey in the U.K., have published a case series in 20 something very preterm infants showing that most of the time, in their units, in their experience with using high-flow, that can be a successful method of stabilization. It’s not a randomized trial, and it’s a small case series.

Brett Manley: We’re not using high-flow in the delivery room. It’s something I’d like to look at, and that’s where surfactant would come in again. Whatever mode of support you want to give to the baby, and then give them surfactant, I think you’re gonna increase your chances of subsequent therapy being successful. In our delivery rooms, extremely preterm infants are managed with Neopuff fire mask. If they’re spontaneously breathing, they’ll go onto CPAP followed by nasal prongs. And that’s how they’ll be transported to the neonatal intensive care unit.

Brett Manley: If they’re not spontaneously breathing, despite resuscitative efforts or have a very high oxygen requirement, they’ll be intubated. We’re not normally giving surfactant in the delivery room unless absolutely indicated (i.e., the baby was hypoxic despite 100% oxygen). Usually we’d wait until the intensive care unit. If the baby went up to the unit intubated, and I’m talking extremely preterm infants, they would all get surfactant in the first few hours of life if not sooner. But wherever we could, we would leave a baby on CPAP support in those first hours of life, and see how they go until they reach whatever our criteria for intubating and giving surfactant are.

Amir Kugelman: We are not using high-flow in the delivery room. Usually we use the Neopuff, and the baby has to go to unit with support, he’s going with NIPPV, using the nasal prongs where we started to use the RAM cannula to take the baby to the unit. We are currently not using high-flow in the delivery room.

Michael McQueen: Brad?

Brad Yoder: We do not use high-flow in the … Well, first of all, we don’t even go to the delivery room. Our units are set up so that the delivery rooms are right by our NICU. So we actually admit the babies directly into the NICU and resuscitate them on their bed.

Michael McQueen: Outstanding.

Brad Yoder: And then we don’t have to move them anymore. I think the … Again, Peter Reynolds has reported really good success. It’s important to understand how he does it, and I’ve talked with him about it. He does not have equipoise in terms of wanting to do a trial because he feels like he has had a lot of success with it. I think a trial needs to be done. Given that he has had some positive results with his, it would seem like that would be, to me, an acceptable trial to entertain.

Brad Yoder: It may also relate back to CPAP alone or nasal INV alone, is that, what he does, it’s the very first thing he does. When the baby comes out, he’s actually applying that therapy even as the baby’s beginning to try to take their first breath. There’s none of this suctioning, stimulating, drying. It’s so that the support is there as soon as that baby breathes, and it’s pretty clear from most of the animal studies that have been done and even from some of the small human trials that have looked at it with electrical impedance tomography, that the baby’s breath is much more effective than our ability to bag mass breathe for them. If you have that support in place, you’re probably going to be more effective than if you don’t have it in place. And if you even wait three, or four, or five, or six breaths … Quite honestly I get a little frustrated when it takes us 30 seconds to put CPAP on … Why don’t we have that CPAP on that baby as soon as we get them on the bed, and that’s the first thing that they get. Again, supporting them.

Brad Yoder: So we don’t use it. I think it should be studied. I think there’s the potential. It’s surprising how small a base population he’s actually been able to find efficacy with his approach. But if it’s gonna be done, it’s gonna have to be done really paying very careful attention as to how you’re applying it, when you’re applying it, and what else you do. Cause it’s not just one therapy. It’s all of these things that we do together that really contribute to the outcome that we’re trying to prevent in the long run, which is generally BPD.

Amir Kugelman: And, of course, it should be compared to methods that use NIPPV or CPAP to the baby.

Brad Yoder: Yeah, absolutely.

Amir Kugelman: For the babies, after the delivery when they are full with fluids … You can’t compare high-flow to no support.

Brad Yoder: No, no, no.

Amir Kugelman: You have to compare high-flow to CPAP and NIPPV.

Brad Yoder: Yeah, I agree completely.

Michael McQueen: Well, all of us have in common, trying to be as least invasive on the infant as we can, minimize support. And as we develop the different arrows in our quiver and the technology and techniques to do that, you know, it’ll be fun to watch this evolution.

Michael McQueen: Again, I can’t thank the three of you enough, and I mean this sincerely, for the contributions that you have made and are continuing to make. In terms of giving your time on this discussion panel … These gentlemen have come from across the globe. They’re jet-lagged, they’re tired, and they’re in high demand. So, I very much appreciate you taking time for this.

Brad Yoder: We have been able to take our preterm lamb model and completely noninvasively support them.

Brett Manley: From birth?

Brad Yoder: No. We do, I don’t want to call it minimally invasive, but I guess it’s minimally invasive.

Michael McQueen: So, how do you do it?

Brad Yoder: So the nice thing about the lambs, you can deliver the lamb and bring his head out, do anything you want to him while he’s still attached to the fetal circulation and doesn’t care. And so they get a little tiny cannula that gets put in, similar to this less invasive, minimally invasive, surfactant thing. Then we deliver them. Then we have a cone mask that goes over them. We use, it’s actually a modified high-frequency nasal ventilation, with sustained lung inflation in there. And then depending on what criteria they meet, at some point in time, if they require surfactant, they get it through this little cannula, but we never intubate them. And then subsequently that cannula would come out and then we just try to continue them on.

Brad Yoder: Eventually they end up … Our target is at 15 minutes by 30 minutes, having them completely on a nasal pharyngeal tube, with high frequency nasal inhalation. We use the Draeger high frequency … We can use that in the lamb. We can’t use it in humans, but we can use it in the lamb. We support them with that.

Brad Yoder: Boy, they have nice looking lungs when they’re all done. But it’s taken a lot. We use fairly large doses of caffeine, but I know you guys, or the group down in Melbourne, has been using some Doxapram as part of that.

Brett Manley: In the animal studies. Yeah.

Brad Yoder: Yeah.

Michael McQueen: For my experience … And, again, I’m one of those whose not nearly as published. I’ve done some collaborative publishing, just thanks to the graciousness of you all including me in some of these. It’s harder from a community facility. Some of them have IRBs, some of them don’t. Some of the systems have IRBs, in fact, I would say all the systems have IRBs, and there’s certainly access to it. Funding, for a non-academic center, is essentially non-existent. That’s where places, like Vermont Oxford, have been really valuable for us to be able to collaborate under an umbrella like that and do some trials. And it’s true. You get incredibly committed to what you’re doing. I watched the machinations that the gent from Columbia went through on affixing the CPAP interface, and thought: “Only if you’re committed to that, would you go to all that.” They spend as much time trying to make sure the CPAP interface is there and not damaging and not traumatic, as they do delivering the therapy. It was remarkable.

Michael McQueen: I tip my hand. For me, the difference was changing the patient population from a surfactant deficient one to a surfactant treated one. We don’t do it prophylactically anymore. We used to do that fairly routinely. There was a time, correct me if I’m wrong, where that was recommended for babies less than 28 weeks or something. But if they have severe retractions, if their x-ray looks granular, if their FiO2 has gone from 25 to 30% in the last hour and a half, we don’t wait. We know what’s coming. He’s gonna get worse. Let’s don’t let him. And then give the surf extubate right away has just had incredible success.

Michael McQueen: I think part of it is the fact that the nurses are so bought in. There was a year when Vapotherm was taken off the market, 2006 to be precise. And, in a way, that sealed the deal on all of my NICUs. The nurses went crazy. They hated that we had to go back to nasal CPAP. We still use that, by the way. We use RAM cannula, we use the ventilator, we use the [inaudible], we use all the arrows in the quiver. But from a noninvasive standpoint, I can hardly wait for aerosolized surfactant to be widespread. You guys know anything about that, that you can share? Is it coming?

Brad Yoder: Takes a long time. Takes hours to-

Michael McQueen: To administer?

Brett Manley: I missed the talk yesterday. Was anyone at the talk?

Brad Yoder: I wasn’t.

Amir Kugelman: He didn’t talk about the time needed, but I’m sure it’s a lot of waste of surfactant because we saw everything in the field that was demonstrating with surfactant that came out of the nose during the … There’s a lot of waste because it doesn’t go only to the lungs.

Brett Manley: And the other interest with MMAs is that laryngeal mask airways just plugging the upper airway and see what happens.

Michael McQueen: That’s intriguing. What a-

Brad Yoder: I mean, I’m really fascinated with that less invasive technique. And I’m always … When people are doing trials and I get one of them, I’m saying: “Okay, now how do you guys do this?” Because we have residents, they don’t know how to intubate. We have NNPs, half the time they don’t know how to intubate. I think it really takes somebody who’s a skilled intubationist to be able to sit there and have it in position and do it while this baby’s on CPAP.

Brett Manley: Yeah, it can be tricky.

Brad Yoder: It is tricky.

Brett Manley: It absolutely is tricky, but the centers that are used to doing it, it just becomes standard.

Brad Yoder: Yeah, I think the data clearly supports that if you can do less invasive ventilation-

Amir Kugelman: It seems to be the future.

Brad Yoder: …and you use the less invasive surfactant in combination with noninvasive support, you’re gonna get the best outcomes.

Amir Kugelman: Yeah, the babies in 30%, in the previous studies, we waited until the baby was in 50%, and then only we intubated and we give surfactant. Now, if you give a surfactant noninvasively when he’s 30%, maybe the babies might be better.

Brett Manley: It’s interesting that-

Brad Yoder: Are you doing noninvasive … Are you part of their study?

Amir Kugelman: Yeah, we are part of the study of.

Brett Manley: … Which probably finishing soon. But we’re introducing mist, we’re calling it, same thing, in our more mature babies. But interestingly, the oxygen threshold for failure comes down because the complication is less. You’re not putting the baby on the ventilator. So why not give the surfactant early? It’s a combination of not only giving the surfactant but giving it earlier.

Amir Kugelman: Still it’s a worry. If you decide if the baby is sitting, let’s say on 35%, and is doing relatively okay, just heart rate and respiratory rate are a bit increased and some retractions, you see they usually calm down and be okay. If you try to play with the surfactant with INSURE, there’s always the question if the babies are going to suffocate. And if you’ve made a decision it doesn’t go where you decide to intubate, but he’s doing bradycardia, or you didn’t succeed with the surfactant going into the lungs, it went into the stomach instead of into the lungs, and then you decide to be more invasive … Instead of going to 50%, not touching the baby, calming down, you’re just trying to intervene. And usually we have residents at night, so if the baby’s at 35, 40% … He’s not really … If he’s not in a study, I’m not going to touch him. So, I can go in the morning and decide. Cause this is practice in life. If it’s in a study, if it’s more than 30%, then go on and maybe I’ll come in. So that’s why it’s important to-

Brad Yoder: So, that was my question: Who’s doing it?

Brett Manley: As we introduce it, it’s the consultants. It’s the attendings, and we’re gonna roll it out eventually to the fellows, the advanced trainees. But it will be a consultant thing at the moment.

Brad Yoder: And I think it has to be. It’s how I would perceive it in our center. It would have to be the attendings doing it to begin with.

Michael McQueen: I think it almost has to be, to start. It is a patient at the end of the trial. We gotta be safe.

Brad Yoder: And then is your study with CPAP or with nasal ventilation?

Brett Manley: The Optimist Trial’s using CPAP-

Amir Kugelman: Yeah, but you’re allowed support of the Optimist- Or allowed to use NIPPV?

Brett Manley: Sorry, or NIPPV.

Brad Yoder: It’s your center preference. Is that what it is?

Amir Kugelman: I went into the study because this is a way to learn the method.

Brad Yoder: Yeah, no, I think it’s a great idea.

Amir Kugelman: It obliges you to go into it. If not, then it’s never convenient. But if it’s in a study and more than 30%, you have to do it.

Brad Yoder: I attempted to see how I can bring it into our practice, but I’ll wait until your study’s done. Hopefully.

Brad Yoder: The thing we’re gonna be doing now … We’re gonna be starting a trial with the nasal jet ventilation compared to nasal ventilation with standard CPAP prongs.

Amir Kugelman: Peter Remsburger is doing a study with nasal high frequency international studies with CPAP.

Brad Yoder: Yeah, I don’t know what his interface is. Do you?

Amir Kugelman: He’s using natural RAM cannula, using the [inaudible].

Brad Yoder: We’re gonna be using a nasal, soft nasal therapy which is what we’ve used.

Amir Kugelman: We usually don’t use it. We use the binasal prongs.

Brad Yoder: Yeah. We’re using binasal prongs for the noninvasive, for the standard nasal ventilation. But what we use in our preterm sheep, is we use a single nasal pharyngeal tube, and it works really well.